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Results for “LTA4H”

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PubMed2026

Host eicosanoid signals define a granuloma fibroblast population that coordinates mycobacterial containment.

Genetic variation at the leukotriene A4 hydrolase (LTA4H) locus is associated with tuberculosis (TB) severity and outcome. Here, we define a unique population of peripheral fibroblasts at the mycobacterial granuloma, the central immune structure in TB, whose recruitment and functions are coordinated by lta4h-dependent signals. Using single-cell profiling of zebrafish mycobacterial infections, we identify a layer of lta4h-dependent recruited fibroblasts at the granuloma's edge with mesenchymal and stem-like expression signatures, including aldh1a3 expression. Ablation of these cells compromises bacterial containment at the structure's periphery. Similarly, genetic disruption of apolipoprotein D, produced specifically in granuloma-associated fibroblasts, results in an altered eicosanoid balance, decreased inflammation, and increased dissemination of infection. In humans, this granuloma-associated fibroblast population is distinct from myofibroblasts, interacts with LTA4H-expressing macrophages, and is prominent across diverse TB granuloma types. These results link a host genetic susceptibility locus to the recruitment and function of a specialized fibroblast population that limits bacterial dissemination.

Animals↗

PubMed2026

Potential evaluation of SULT1A3 as an early diagnostic marker for nasopharyngeal carcinoma: a study based on serum proteomics screening and ELISA validation.

BACKGROUND: Nasopharyngeal carcinoma (NPC) represents a highly prevalent and aggressive malignancy endemic to Southeast Asia. Early and accurate diagnosis is critical to improving survival outcomes; however, the absence of robust, stage-specific biomarkers remains a key obstacle to clinical implementation of early screening strategies. METHODS: We performed untargeted serum proteomic profiling using mass spectrometry in 15 treatment-naïve early-stage NPC patients and 15 VCA-IgA-positive healthy controls. Bioinformatics analyses were conducted to identify differentially expressed proteins (DEPs). Machine learning (random forest combined with recursive feature elimination) was employed to prioritize candidate biomarkers, which were subsequently verified using enzyme-linked immunosorbent assay (ELISA) in independent sample cohorts. RESULTS: In total, 1,428 serum proteins were identified, among which 1,410 were reliably quantified. We observed 31 upregulated and 189 downregulated proteins in NPC patients relative to controls. Spearman correlation analysis revealed significant associations: LTA4H (leukotriene A4 hydrolase) levels correlated with serum cell infiltration (r = 0.383, p = 0.032) and CD8 + T-cell abundance (r = 0.408, p = 0.021); both SULT1A3 (sulfotransferase family 1 A member 3) and FGL1 (fibrinogen-like protein 1) levels were positively associated with M1 macrophage infiltration (r = 0.510, p = 0.003 and r = 0.430, p = 0.015, respectively). In a preliminary validation cohort (n = 80), ELISA yielded AUC values of 0.631 (95% CI: 0.515-0.736, p = 0.04) for LTA4H, 0.787 (95% CI: 0.681-0.871, p < 0.001) for SULT1A3, and 0.688 (95% CI: 0.575-0.787, p = 0.002) for FGL1. In large-scale independent validation, SULT1A3 achieved an AUC of 0.826 (95% CI: 0.766-0.876; sensitivity = 78.89%, specificity = 75.47%) in cohort 1 (n = 196) and 0.796 (95% CI: 0.723-0.857; sensitivity = 76.67%, specificity = 76.67%) in cohort 2 (n = 150). CONCLUSIONS: Through an integrated workflow combining proteomic screening, machine learning prioritization, and multi-stage ELISA validation, we identified SULT1A3 as a candidate serum-based biomarker for early detection of NPC. Preliminary findings suggest that SULT1A3 may have potential utility in clinical screening, though further validation in independent, multi‑center cohorts is required.

Humans↗

PubMed2026

Integrated transcriptomic and metabolomic analyses reveal key regulators associated with lipid metabolic differences between subcutaneous and visceral adipose tissues in sheep.

The location of fat deposition has a significant impact on meat quality and body health, and different adipose tissues exhibit significant differences in lipid metabolism and immune regulation. This study aimed to systematically compare the phenotypic characteristics, transcriptome, and metabolome of subcutaneous adipose tissue (SAT) and two types of visceral adipose tissue (VAT) in sheep, in order to reveal the metabolic differences between SAT and VAT and their potential regulatory mechanisms. The results showed that compared with VAT, SAT had stronger triglyceride deposition ability and obvious cellular hypertrophy. Through integrative analysis, 15 key lipid metabolism genes and 12 differential metabolites were identified. Among them, ACACA, FASN, ELOVL6, SCD, as well as metabolites palmitic acid and glycerol-3-phosphate, may play a central role in SAT lipid synthesis and storage; whereas IGFBP2, ADRB3, LTA4H, and metabolites arachidonic acid and leukotriene B4 may be involved in the lipolysis regulation and inflammatory response of VAT. These findings may provide deeper insights into the regulatory mechanisms of fat deposition in sheep.

Animals↗